Dr. William Kannel, director of the Framingham Heart Study during its early years, discusses the innovations introduced in this first-of-its-kind study which began in 1950 and its tremendous legacy. The Framingham Study changed not only the way heart disease is perceived and treated, but also the way medical studies have been conducted ever since.

The Framingham Heart Study: Cornerstone of Modern Heart Disease Research

INTERVIEWER: When you first came to Framingham, Massachusetts, in the relatively early days of the study, what was known at the time about the causes of heart disease?

KANNEL: The Framingham Study was put into effect to determine how those who go on to develop heart attacks and strokes differ from those who manage to escape them over a long period of time. At the time the Study was initiated, which was 1950 or so, there was very little known about the causes of cardiovascular disease, but there was recognition of a rising epidemic of coronary disease in particular, so the United States Public Health Service initiated this epidemiological research. This was really rather innovative, because formerly, that approach had been applied chiefly to infectious diseases.

INTERVIEWER: We take this kind of study for granted now, but at the time, this was completely uncharted territory, was it not, to put this many people together in one place and to get them to agree to keep on doing this for that long a period of time? How did you think that you were going to be able to pull that off?

KANNEL: Well, this was a rather unique and formidable task. At that time, studies of disease were confined to case-control comparisons. One study identified a dozen cases and matched it with a dozen or so controls and looked at any differences that might be present to give some clue as to what was going on. In the initial design of the Framingham Study, we were charged with the task of following 52,009 people over more than a 20-year period. The goal was to measure the relationship between a set of hypothesized predisposing causes against the actual development of the disease by subjecting each of the study participants to a clinical examination once every two years.

This was a new approach, because we had something like 80 variables to apply to this task and no computers, no copy machines. We were supposed to do this all by hand, using carbon paper and electric typewriters and an abacus for counting and doing statistical analysis. We had a primitive punch-card apparatus that did counting and sorting. The machine that did this was as big as an upright piano. It clanked away for eight hours to count and sort what a computer could now do in two seconds. Fortunately, we were rescued when technology started to come along that made this [kind of analysis] actually feasible.

INTERVIEWER: We live in a computer age, and people take dealing with a lot information and a lot of data for granted, but this really was the first time where a study this complex had been done. Did you ever feel, "I don't know if we can do this"?

KANNEL: Oh, yes. We soon learned that we had a formidable undertaking when we started compiling the data and tried to analyze it using the tools we had. One of the problems that came up very early was how to deal with multiple interrelated factors. The statistical methodology at that time was that you cross-classified; you looked at people with A at given levels of B. [But when you] say, OK, we're going to do this with 80 different things and [look at] different sexes, different ages, different levels of blood pressure, different levels of cholesterol, then how do we do this? That was a stimulus to the development of multivariable analysis, and we went back to Bethesda, [Maryland], to the National Institutes of Health, where we had statisticians, and said: "Guys, you've got to help us out here. We don't know how to do this. How do we assess the net and joint effect of multiple interrelated factors?"

They then began to develop methods for multivariable analysis. So our problem generated the statistical methodology that was necessary to do the kind of analysis everybody does today. That was a very important feature of the evolution of epidemiological investigation, looking into the net and joint effect of different predisposing factors for disease.

INTERVIEWER: So you literally invented it as you went along?

KANNEL: We had to invent everything as we went along: the follow-up methods; the technology for analyzing data; the way to connect with the population and correct the data problems that we had as we evolved, and how to innovate [using] the new technologies as they came along. As [each] new technology came along, we introduced it to better evaluate what was going on—new imaging techniques, for example: From electrocardiography we went to echocardiography, [then] onto CAT scans. All sorts of technologies were added to further fine-tune and refine our observations, because to stay in this business, which costs a lot of money and is work-intensive, you have to stay at the forefront. Otherwise you're not going to get funded.

INTERVIEWER: Looking back at the early years, what do you remember as the biggest problem? Was there a moment where you thought, "This whole thing is going to fall apart"?

KANNEL: Well, early on, we as investigators were eager to see the results, and our statistical people in-house were saying: "What do you expect us to do? We're working as fast as we can." But we were very impatient and not particularly attuned to sitting back and waiting 10 years while we just examined patients; we wanted to report [the findings]. In order to deal with that, what we did was to begin cross case-control comparisons, comparing people who already had the disease in comparison with the rest of the population that didn't, and this gave us clues to follow.

INTERVIEWER: We know you were not in Framingham at the very beginning, but as we understand it, when people started to be recruited, you had to get just about half of the adults in the proper age group in the town to agree to do this.

KANNEL: Yes. The statisticians determined for us how large a sample we might need, and they wanted it to be fairly representative of the population of Framingham. They indicated the number we needed to get, and we [were able to get] about two-thirds of that. Because people were walking into the unknown and didn't want to appear to be a guinea pig to be experimented on, we had to earn their trust, and we did this by face-to-face persuasion, by having the leaders in the community go through the exam [first] so they would know firsthand what was involved. Then they would go back and see the people in their neighborhood and by face-to-face persuasion get them to agree to participate. We [also] elicited the support of their physicians in town, and had the physicians also [become] part of the sample so they could firsthand determine whether this was something they wanted their patients to participate in.

INTERVIEWER: You must know two of the people that we've interviewed, Evelyn Langley and Victor Galvani.

KANNEL: Yes.

INTERVIEWER: Tell me the role that people like that played in getting this off the ground.

KANNEL: Well, they were essential in getting us organized, getting us started, and maintaining the population support for the epidemiological observations and research. They've continued to participate, [and] the loss to follow-up [has been] trivial.

Follow-up loss is the Achilles' heel in long-term studies. If you lose too many, it makes it very difficult to claim you really have unbiased data, and this was essential. This study has been going, as you know, for more than 50 years, and we've maintained the support of the population, which we've been very grateful for.

INTERVIEWER: The first paper about the Study came out about six years after it began?

KANNEL: Yes. This type of study is a waiting game. You make measurements of the characteristics of the people you're following and then wait for them to get sick or not get sick. That does not accumulate very rapidly, fortunately for the population. But cardiovascular disease is a very common and lethal disease, and the events began to come in. Early on we got some indications of important things that were evolving, and we reported these as they appeared, in order to give everybody a leg up on what was happening and to start looking at ways that we might modify these characteristics.

INTERVIEWER: The first term that you used, which now we all know, was risk factors.

KANNEL: Yes. Epidemiological research, I think, gives us two kinds of insights. One kind is the insights into the pathogenesis of the disease, the mechanism. Those insights tell us what is going on and give clues to [guide] more basic research; animal experiments and very detailed studies of the metabolism of disease, for example.

Epidemiological research also allows us to craft risk profiles so we can pool information together and be able to better identify high-risk subjects [and] determine the conditional probability that they'll have an event by [looking at] the battery of risk factors they have. [We can then look at] what the potential is to lower that risk if we can correct these risk factors.

[About six years after the Study began], I had written a paper, and I said that we were looking at "factors of risk" important in the development of cardiovascular disease. That then became "risk factors." So it is a term that's now been accepted universally and applied to all sorts of chronic disease.

But I think there's a [key] principle behind this: Formerly it was thought that disease evolved from a single, essential cause that was sufficient, by itself, to produce the illness. We now know that's not true. [Instead], there are important factors, and in chronic diseases there appear to be multiple interrelated factors which by themselves are not necessarily going to produce the disease. [We now know] that risk factors for cardiovascular disease, for example, cluster, and [it is] as an aggregate [that they] tend to produce the disease. This [statistical information] has led us to produce multifactorial risk profiles that allow us to assess a person's risk based on multiple characteristics they have.

INTERVIEWER: It must have also been a huge change in the general way of thinking about heart disease, because as we understand it, before the Framingham Study started, people thought of a heart attack as just a lightning bolt; it came out of nowhere.

KANNEL: Yes, and there was a concept that it was an inevitable [result] of aging and genetic makeup; that if you had a bad family history, that was it. We began to say, "No, it isn't exactly that way; some folks are more susceptible than others, and there are correctable, predisposing causes that can be dealt with to lower the risk." This was an important contribution.

Heart Disease Risk Factors: High Blood Pressure

INTERVIEWER: One of the first risk factors that you identified was blood pressure.

KANNEL: Yes, we established fairly well that elevated blood pressure was a distinct risk. When we started out, hypertension was divided into two major categories: malignant hypertension and benign, essential hypertension. Now, the term "benign, essential hypertension" had a connotation; namely, that it was not terribly important, and that it was essential for people's blood pressures to go up as they got older in order to [sufficiently] profuse their organs [with blood] through narrowing vessels.

Well, we showed it was neither benign nor essential, and that in fact the elderly were at even greater risk when they had an elevated pressure. The other misconception about hypertension that I think we corrected was the importance of systolic blood pressure, [the pressure generated when the heart contracts], versus the diastolic pressure, the pressure that exists between contractions.

It was felt, at that time, that the evil consequences of hypertension derived from the diastolic component, and this was a very aggressively held notion by many physicians. We showed it simply wasn't correct. [Instead], the systolic pressure was more important, and was important no matter what the diastolic pressure was. Then [we] eventually [showed] that the pulse pressure, the difference between the systolic and diastolic pressure, was also important.

So we got rid of the notion that hypertension was benign or essential, and in fact, we found that it was actually very basic to the atherosclerotic process [the thickening and hardening of artery walls from accumulation of fatty deposits on their interior lining]. I had our pathologist do a section of a vessel in a person who had died and had an autopsy comparing an artery and a vein side by side. The artery was completely blocked by atheromatous deposit; the vein was completely open. What's the difference between these? One was [a vessel for] low pressure circulation; the other was [a vessel for] high pressure circulation.

If you want to see atherosclerosis in a vein, just take it out and bypass a coronary artery and put [the vein] in the systemic circulation, which is high pressure. You get atherosclerosis in veins. To me that demonstrated [that pressure] was a critical facto. That's now quite commonly recognized, although in treatment, I must say we've been disappointed that physicians still treat diastolic pressure better than systolic blood pressure.

INTERVIEWER: Translating that into the [blood pressure] numbers that a physician or nurse reports to you when your blood pressure is taken, which is the number on the top, and which is the number on the bottom?

KANNEL: If [your blood pressure reads as] 130 over 80, 130 is the systolic pressure and 80 is the diastolic pressure. It's the top number that really matters the most.

INTERVIEWER: Going back to the traditional view that as you aged, your blood pressure was supposed to go up, was there a lot of resistance when you first came out with the finding that an increase in blood pressure as you got older was actually not good for you?

KANNEL: Oh, there was. In fact, very recently a statistician came up and said, no, this was all wrong, and that we needed different criteria for our hypertension for elderly people than for younger people, and that there were actually critical values. But all the evidence showed very distinctly that this is a continuous, graded influence; that it is blood pressure that kills, not "hypertension," as there are no critical values, and Dr. [Ramachandran] Vasan here [in the Framingham Study] showed that within the range of blood pressures we consider normal, risk increases with the blood pressure level. I think all the evidence we've collected now shows unequivocally that there's a continuous graded influence, incremental without critical values.

INTERVIEWER: Has this been a pattern with all of the Framingham discoveries, that as one discovery after the other has come out, people have said, "That's not true"?

KANNEL: There's a French physician whose name I don't recall who put it this way. He said this is the way research progresses: Whenever a new discovery is made, the scientific community's first response is "It's probably not true." After a while the truth emerges and is accepted; then their response is, "Well, it may be true, but it's not important." After a while, they find it is not only true, but important. At that point, the response is, "Well, it's no longer new, so who cares?"

That's the way all the findings have gone. We had to fight our way and remind people repeatedly of the finding, and then eventually they say: "OK, yeah, we agree. So what does it all amount to? Now we know this, so why are you telling us this again?" Changes occur by evolution, not by revolution, and you have to keep pointing things out from different aspects and points of view, and finally they get accepted. But to change die-hard concepts is not an easy thing to do.

INTERVIEWER: But you would think that with heart disease being such a huge problem in this country, being the number one killer, and with so many people suffering from it, and even when they've survived an initial heart attack, being forced to continue to live with heart disease or congestive heart failure, you would think that physicians would be thrilled to have new information that they could apply to their patients.

KANNEL: Well, they are, and they do [try to] keep up with it. But as you know, new information is evolving in a logarithmic way; it's just piling in faster than people can take it in. The problem is translating research information into clinical practice. People tend to fall back on the way they've always done things, and it takes them a long time for it to translate [new research findings] into changes in practice. There's a disconnect there that needs to be corrected.

Heart Disease Risk Factors: Smoking

INTERVIEWER: One of the next big findings that surprised many people was the finding about smoking.

KANNEL: Oh, yes. Based on early studies, smoking was recognized as a bad practice for lung cancer, emphysema, and chronic bronchitis, [but] I wrote an editorial sometime later and said we're missing the boat; it's an ever bigger problem for cardiovascular disease. Yes, there's a tenfold increased risk for lung disease and maybe only a twofold increased risk of cardiovascular disease, but there are at least 10 cardiovascular events for every case of lung cancer, and therefore, more disease attributable to smoking occurs in the cardiovascular area than in the lung area.

It took a while for that to be accepted. Of course there were powerful, vested interests that were against us [publicizing] that. The tobacco industry's position was, well, there's nothing harmful in cigarette smoke, and that's why we're filtering it out. They had this position where they were producing filter cigarettes and claiming there was nothing harmful in cigarette smoke. Amazing.

Heart Disease Risk Factors: Obesity

INTERVIEWER: Another finding that was surprising to people when the paper came out was that being overweight was a risk factor all by itself.

KANNEL: Yes. Not only in that, but there were actually papers in The New England Journal of Medicine for a while implying that being overweight was not a risk factor. The implication was that if you adjusted for the covariants, there was nothing left for the obesity itself. Well, that's nonsense. [That's just] statistical numerology, because we showed that as people gain weight, their blood pressure gets worse, their cholesterol gets worse, their diabetes risk goes up, and so on. That's what [obesity] does. It operates by producing these things, and if you adjust for it, OK, so there may not be [as much of a risk factor] left, but that doesn't mean it's unimportant.

[At present in this country,] we have a virtual epidemic of obesity and overweight because we've engineered physical activity out of daily living. We've got [an overabundance] of food and drink. People eat for entertainment, not to stay alive. We have no portion control; everything has to be king-sized. You go to Europe, you get a little piece of meat that's sprinkled on some pasta. Here, we get a chunk of meat and along with it, the other stuff on the side. We've got it backwards, and we need to do something about that, but that's a cultural change that has to take place, and it takes a while to evolve.

Risk Factors and the Development of Drugs

INTERVIEWER: What impact, if any, did the identification of these risk factors have on the pharmaceutical industry?

KANNEL: [The establishment of a battery of risk factors for cardiovascular disease] provided a stimulus to the pharmaceutical industry to develop remedies. Now that they had the evidence, they said, OK, we've got a drug that corrects the predisposing factor; now let's mount a trial to demonstrate that it does so, and then we can sell the drug. Why would they be so interested in investing that much? Well, you're talking about huge segments of the population with high blood pressure and bad cholesterol.

Normal vs. Optimal Risk Levels

KANNEL: One of the things that was also basic that we learned was that what was usual in a population was not necessarily optimal. We used to define blood pressure by what was the average in the population, high cholesterol the same way, and so on. Well, it turned out that we were in a population with extraordinarily high levels of cholesterol, and what we were calling normal, what was usual, was not optimal at all, and we began to propose optimal levels.

We proposed it way back then, but it took maybe 20 years for everybody to get around to accepting the new [guidelines]. And if you notice [those] guidelines, they keep lowering the level at which you have an acceptable risk factor profile. I once saw a cartoon in which the doctor says: "Oh, I have some bad news for you, Mr. Jones. Your cholesterol has remained the same, but the risk factor findings are changed." They do keep refining it, redefining it down to lower and lower values, so what you were told 10 years ago was acceptable, now the doctor has to tell you that's not acceptable; you've got to do something about it.

That's happened, I think, with blood pressure, with lipids, with glucose, with almost every risk factor. The guidelines produced by the organization have been pushing those levels down, and I think that's been a product of epidemiologic research, such as that at Framingham, where we were looking for optimal, rather than usual.

INTERVIEWER: But shifting those guidelines has been another battle, hasn't it?

KANNEL: Yes, it has, but that's the way research is. Making new discoveries is great and gratifying, but—how do you say it? The [researcher's] cup of joy is full when these findings are put to immediate use. And the thing that's encouraged us is that the [Framingham] findings have been put to use, and that has, I believe, started to lower the rates of disease in the population.

Preventing Heart Disease

INTERVIEWER: You said it was frustrating as a researcher to wait for 10 years to get your results, but you're also a doctor, trained to take care of people. It must have also been frustrating to see people dying of heart attacks while you're still searching for causes, you're still searching for risk factors, and there's nothing you can do yet to prevent those deaths.

KANNEL: Well, we once pointed out that we have to think of the occurrence of a heart attack or a coronary or a heart failure not as the first indication for treatment, but really as a medical failure, because this [condition] should be detected on its way to happening and be corrected before that point. That's the concept that I was trying to get across: that you shouldn't sit and wait for the catastrophe to occur; you should head it off at the pass, so to speak.

INTERVIEWER: But in the early days, you didn't have any way to do that?

KANNEL: No, until we learned the way the disease evolved—what factors were leading to it and whether these could be corrected—then we had to find evidence that if, in fact, you corrected them, you did affect the course of the disease. And we began to develop that. That caused the whole evolution of this concept of evidence-based medicine, in which you no longer talk about clinical impressions or theories; you want to be shown the evidence.

INTERVIEWER: Was the idea of preventing noninfectious diseases a new concept in medicine?

KANNEL: Preventive cardiology didn't exist when we started. Everybody was merely thinking of how to deal with this inevitable consequence of aging and genetic makeup. There wasn't any concept of preventive cardiology, and I think epidemiology has become the basic science of preventive cardiology.

Why Does Heart Disease Remain an Epidemic in America?

INTERVIEWER: Why do you think it is that now, almost 60 years later, with all of these findings and all of the evidence and incontrovertible studies that have come from Framingham and other places, that we still have an epidemic of heart disease in this country?

KANNEL: Well, maybe because we haven't gotten into the act early enough in life. Maybe we need to think about this disease as a pediatric disease and start curbing the evolution of risk factors [before people age and are exposed to noxious influences]. If we head it off earlier on, then [we may] begin to see it decline. Once somebody's been exposed to hypertension for 20, 30 years, I don't think you can turn it off just like you would a light switch. Also, I suspect there are other yet-undiscovered causes, and that we may be dealing with a time-dose product of risk factors.

A little risk factor for a long time may be bad, and a lot of it for a short time may be bad, and they may be equivalent. Everybody has blood pressure, everybody has lipids, and everybody has fat and so on, and therefore, it's just a time-dose product. It's almost a lifestyle issue. You've got to change the whole culture.

INTERVIEWER: But do you think that's possible? People know what they should do now. All these findings come out from Framingham, and we know we're supposed to exercise; we know we're supposed to eat healthy, but ...

KANNEL: Yes, it is true that people have difficulty, despite the knowledge that's out there, because we're asking them to swim upstream against their culture. We've engineered physical activity out of existence. We've enriched the diet with lots of fat and cholesterol and too many calories, too large portions [of food]. When you go into a restaurant, unless they give you a chunk of beef that you can milk, you feel you've been cheated. I have a cartoon I show the students of a waitress asking her customers, "Will you have that with or without an angioplasty?"

The fact of the matter is that people have trouble following this. Another cartoon I like is one in which a son asks his father, "What does 'cholesterol' mean?" The father says, "I don't know; I think it's Latin for 'flavor.'" People have the perception that these lifestyle changes are unpalatable, but let's face it: What's being recommended is an Oriental or a Mediterranean diet.

Now, I think Italians are congenitally unable to produce a bad meal, so I don't know what all the fuss is about. If people knew what they were doing, they could eat well, enjoy everything they eat, and still be heart-healthy. But the problem, as I pointed out earlier, [is that making these changes is] swimming upstream against the culture. The vested interests are trying to give people what they think they want, and they're not necessarily healthy things. It took us how long to get rid of the cigarette-smoking habit?

It's going to take a long time to redesign the whole culture. If we knew how to keep cultures compatible with each other, we wouldn't have the current mess we're in with terrorism, so you know, yes, it's a difficult problem, and not one we can deal with in a very superficial way.

Can Heart Disease Be Cured?

INTERVIEWER: There's another problem that other doctors we've talked to have pointed out. Because of all of the advances in surgery and interventional cardiology, people can survive a heart attack; they can even survive two or three. Look at Larry King, for example; he's survived through many of them. The impression in many people's minds is that you could get a heart attack, and they'll just fix you up, and then you'll be fine. There's not a realization that once you've got heart disease, or any kind of cardiovascular disease, it's not going away.

KANNEL: That's true. I've seen a cartoon in which the doctor says to the patient, "Well, now that you've developed the disease, you don't need to worry about getting it." Well, the fact is you do, because you're now at high risk for another heart attack or associated cardiovascular [event], like a stroke, peripheral artery disease, or heart failure. No, you're not out of the woods, even though you've had a procedure. People think of procedures, like a bypass, as curative. They're not. They're palliative. You're still at very high risk of subsequent disabling and lethal attacks.

Also, one of the things that the Framingham Study did was to show the real picture of cardiovascular disease, including not only things that reach the clinical horizon, but things that occur outside of the hospital and doctor's office. We found that sudden death is a prominent feature of coronary disease. Half of all deaths are sudden, unexpected deaths occurring outside the hospital before you can get there. Now, you can't correct that with surgery. You're dead, right?

The other thing we found [was that] one in every three actual heart attacks went unrecognized. Half of these were completely silent. The other half were so atypical that neither the physician nor the patient even considered the possibility [that they were heart attacks]. So you say, well, if it's silent, why worry about it? An [asymptomatic or atypical heart attack] carries just as bad a risk as a symptomatic heart attack in a patient who survives it. [When it comes to] women, 50 percent of all heart attacks in hypertensive women are silent or unrecognized.

We're talking about something that really requires a preventive approach. If you can have a silent disease without knowing it, and it kills you suddenly, before you can get into a hospital, then you can't wait to have the heart attack, because you may not be the one who's going to get there in time to have the procedure done, and even if you have the procedure done, it's not curative. It's only palliative. This concept needs to be understood.

The Risk of Heart Attack for Women

INTERVIEWER: Let's talk for a moment about women. It's a relatively recent [development] that attention is being paid to the fact that women's heart disease symptoms are often completely different from men's, and not the typical pain in the chest and down the left arm, and many doctors miss the early symptoms of heart problems in [women].

KANNEL: [As I mentioned before,] when it comes to women, 50 percent of all heart attacks in hypertensive women are silent or unrecognized. One of the things the Framingham Study did, because we actually followed the cohort almost to extinction, was determine the lifetime risk of having a coronary event. For a man, the lifetime risk is about 50 percent. For women, it's about 32 percent. That happens to be almost three times the risk of breast cancer, which women fear much more.

Women really have to understand that this is not strictly a male disease; that it affects women as well. And women, as I say, are more prone to these silent heart attacks, and they are more prone to develop angina than an actual myocardial infraction, and their angina, as you just pointed out, may not [present itself in] the same [way as a man's]. A woman may feel dizzy, short of breath, uncomfortable, and not have the same crushing chest pain. Therefore, women need a preventive approach as well, because they could have attacks which occur so atypically that the physician doesn't even suspect [heart disease]. Also, there is sort of a physician bias against women having heart attacks. They tend to think of it as psychosomatic problems. [Doctors] used to say about women with low blood pressure that these were women who had the vapors, fainted a lot. Well, yes, women with low blood pressure may have had these symptoms, but they were virtually immortal, we found. They lived forever, burying two or three husbands, so low blood pressure in women is not a problem or a sign, as they say, of constitutional inferiority. [These women] were people who were going to be around a long time.

[In terms of illnesses, often] women do have an advantage over men. They're the heartier sex for most illnesses, except peculiarly female ones, but they are still vulnerable to all the cardiovascular risk factors, and cardiovascular disease is a very substantial risk for women as well as men.

When they undergo the menopause, they abruptly escalate their risk of a cardiovascular event, and they go from the milder kind of events, like angina, to actual heart attacks and sudden death. So this is not a minor problem for women.

The Legacy of the Framingham Study

INTERVIEWER: You've been connected to the Framingham Heart Study, in one way or the other, most of your life. When you reflect on the study from its beginning until now—all the things that have come out of Framingham, the impact it's had on heart disease, but even more broadly, its impact on the way we think about medicine and disease, particularly cardiovascular disease—what would you say?

KANNEL: Well, I think, in fact, we have made a major impact on the way physicians and researchers approach unknown diseases and approach the problem of preventing disease. We now are willing to examine unorthodox kinds of issues. We're recognizing that progress is not made by the orthodox concepts; you have to look at the unorthodox things. We're not as resistant as we used to be to innovation and new concepts.

We [also] made a major contribution in providing the concept of the evolution of disease as being a subject of multiple interrelated factors that could produce the disease. The risk factor concept, which I think has now been applied to arthritis, dementia, Alzheimer's, cancer, and a variety of other diseases, [has] been an important contribution. We no longer think of a single, essential, sufficient cause, and we now recognize that it's worthwhile to look for correctable, predisposing factors. A lot of studies have been modeled after the Framingham Study and applied to other disease entities, which we find gratifying.

We've also been gratified to find that other studies in different ethnic groups and different countries have virtually replicated Framingham's findings, which gives it biological relevance, and also that the findings are biologically plausible, that they do make sense and therefore are worthy of attention.

INTERVIEWER: What has it been like for you personally?

KANNEL: Oh, it's been wonderful. I've actually wondered, gee whiz, I'm actually getting paid to do [something] that I love so much. And to see what we've done produce useful results, and also to see theories I had actually pan out and turn out to be correct, and to see all the clinical misconceptions that were out there gradually clarified, that has been most gratifying. A lot of people do a lifetime of research and see very few results from it, and I can't say that's been the case in my research. I've actually seen it pay off in all sorts of ways.

INTERVIEWER: What about the original cohort who volunteered to participate in the Study, the few that are left, people like Evelyn Langley and Victor Galvani? They are still coming in, and their children have become part of the study, and their grandchildren, too. Looking back at those original people who got this off the ground, Mr. Galvani said he thinks they have bragging rights.

KANNEL: Yes, they do. I think our surviving cohort have been wonderful and deserve all the credit they can get. It's now a contest actually between the senior investigators and the cohort to see who will survive longer. I suspect they will. So it's been a wonderful experience for both of us, and I think we both are looking back on this with some pride.